POS1177 ROLE OF INTRATHECAL PRODUCTION OF IL-6 IN THE PATHOGENESIS OF CHRONIC PROGRESSIVE NEURO-BEHCET’S DISEASE
Authors: S. Hirohata, H. Kikuchi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Behçet's disease (BD) is characterized by recurrent attacks of aphthous stomatitis, uveitis, genital ulcers, and skin lesions, including folliculitis, erythema nodosum like lesions, and superficial thrombophlebitis. Central nervous system (CNS) involvement is one of the most serious complications in BD and is called neuro-Behçet's disease (NB). There has been accumulating evidence that NB can be classified into acute type (ANB) and chronic progressive type (CPNB) based upon differences in the clinical courses as well as in responses to corticosteroid treatment. Thus, ANB responds well to corticosteroids and usually runs a self-limiting course. By contrast, CPNB is characterized by intractable neuro-behavior changes and cerebellar ataxia, which progress in spite of high doses of corticosteroids or immunosuppressive drugs, including azathioprine or cyclophosphamide. <h3>Objectives</h3> Previous studies have demonstrated that cerebrospinal fluid (CSF) IL-6 was elevated in patients with CPNB. However, little is known as to the mechanism of the elevation of CSF IL-6 in CPNB. The present study was designed in order to elucidate the mechanism of the elevation of CSF IL-6 in the pathogenesis in CPNB. <h3>Methods</h3> Paired serum and cerebrospinal fluid (CSF) samples were obtained from 19 patients with CPNB when they presented active neuropsychiatric manifestations and from 19 control patients with non-inflammatory neurological diseases. Among the 19 patients with CPNB, 5 patients received treatment with infliximab and followed up thereafter. The levels of albumin and IL-6 in CSF and sera were measured by ELISA. Blood-brain barrier (BBB) function was evaluated by Q albumin (CSF/serum albumin quotient x 1,000). The intrathecal production of IL-6 was evaluated by CSF IL-6 indices ([CSF IL-6 x serum albumin]/[serum IL-6 x CSF albumin]). <h3>Results</h3> Serum IL-6 and CSF IL-6 were significantly higher in 19 patients with CPNB compared with control patients with non-inflammatory neurological diseases. Among 19 CPNB patients, serum IL-6 levels were not significantly correlated with CSF IL-6 levels (r=0.0938). As for 5 patients with CPNB treated with infliximab, all of CSF IL-6, serum IL-6, Q albumin and CSF IL-6 indices were significantly elevated compared with control patients with non-inflammatory neurological diseases. Treatment of the 5 patients with infliximab dramatically decreased CSF IL-6 in the next day, but neither serum IL-6 nor Q albumin (Figure 1). Of note, CSF IL-6 indices were dramatically decreased on the next day of treatment with infliximab in the 5 patients with CPNB (Figure 1). <h3>Conclusion</h3> These results indicate that serum IL-6 as well as CSF IL-6 is involved in the pathogenesis of CPNB. More importantly, the course of treatment of 5 CPNB patients with infliximab clearly indicated that the elevation of CSF IL-6 was not caused by blood-brain barrier breakdown, but by its intrathecal production in CPNB. <h3>References</h3> [1]Hirohata S, Kikuchi H. Behçet's disease. Arthritis Res Ther <b>5</b>: 139–46, 2003. [2]Al-Araji A, Kidd D. Neuro-Behçet's disease: epidemiology, clinical characteristics, and management. Lancet Neurol <b>8</b>: 192–204, 2009. [3]Hirohata S, Kikuchi H, Sawada T, et al. Clinical characteristics of neuro-Behcet's disease in Japan: a multicenter retrospective analysis. Mod Rheumatol <b>22</b>: 405-13, 2012 [4]Akman-Demir G, Serdaroglu P, Tasci B. The Neuro-Behçet Study Group. Clinical patterns of neurological involvement in Behçet's disease: evaluation of 200 patients. Brain <b>122</b>: 2171-82, 1999. [5]Hirohata S, Isshi K, Oguchi H, et al. Cerebrospinal fluid interleukin-6 in progressive Neuro-Behcet's syndrome. Clin Immunol Immunopathol <b>82</b>: 12-7, 1997. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.